Methods and uses involving genetic aberrations of nav3 and aberrant expression of multiple genes

Abstract

The present invention relates to the fields of genetics and oncology and provides methods for detecting tumors as well as methods for treating patients and predicting the prognosis to a patient. Specifically, the present invention relates to a method of demonstrating the malignant character of a tumor or cell subpopulation in a subject, to a method of predicting a prognosis, to a method of treating a subject having a tumor with NAV3 copy number change and with over expression of at least one gene or gene product selected from specific lists, and to a method of selecting a treatment to a subject. The present invention also relates to uses of NAV3 gene or gene product and at least one gene and/or gene product selected from specific lists for demonstrating the malignant character of a tumor or cell sub-population, for predicting a prognosis to a subject, for selecting a treatment to a subject, and for cancer therapy in a subject having a tumor with NAV3 copy number change. Furthermore, the present invention also relates to a use of an antagonist, antibody or inhibitory molecule of at least one gene and/or gene product selected from specific lists for cancer therapy in a subject. Still, the present invention relates to a diagnostic kit comprising tools for detecting NAV3 copy number change in a biological sample and tools for detecting over expression of at least one gene or gene product selected from specific lists in a biological sample. The present invention also relates to a use of a diagnostic kit of the invention for demonstrating the malignant character of a tumor or cell subpopulation, for predicting a prognosis to a subject with a colorectal tumor, brain tumor or tumor of epidermal keratinocytes and for selecting a treatment to a subject with a colorectal tumor, brain tumor or tumor of epidermal keratinocytes.

1 - 35 . (canceled) 
     
     
         36 . A method of demonstrating the malignant character of a tumor or cell subpopulation in a subject, the method comprising:
 i) determining a NAV3 copy number change in a biological sample from the subject; and   ii) determining overexpression of at least one gene or gene product selected from IL23R, GnRHR, beta-catenin, and those listed in tables 8-12, in the biological sample or another biological sample from the subject;   iii) demonstrating the malignant character of a tumor or cell subpopulation in a subject, when both a NAV3 copy number change and overexpression of at least one gene or gene product selected from IL23R, GnRHR, beta-catenin and those listed in tables 8-12 are present in the sample(s) from the subject.   
     
     
         37 . A method of treating a subject having a tumor with a NAV3 copy number change and with overexpression of at least one gene or gene product selected from IL23R, GnRHR, beta-catenin and those listed in tables 8-12, comprising a step, wherein at least one gene or gene product with overexpression is affected. 
     
     
         38 . A method according to  claim 37 , further comprising a step, wherein the gene(s) or gene product(s) selected from IL23R, GnRHR, beta-catenin and those listed in tables 8-12 is affected by underexpressing or inactivating the gene(s) or gene product(s) or decreasing amount of the gene product(s). 
     
     
         39 . A method according to  claim 37 , further comprising a step, wherein a gene or gene product of NAV3 is affected. 
     
     
         40 . A method according to  claim 39 , wherein the gene or gene product of NAV3 is affected by overexpressing or activating the gene or gene product or increasing amount of the gene product. 
     
     
         41 . A method according to  claim 37 , wherein at least GnRH and/or JAK/STAT signalling pathway is affected. 
     
     
         42 . A method according to  claim 37 , wherein the method is gene therapy. 
     
     
         43 . A method according to  claim 37 , wherein an antagonist, antibody or inhibitory molecule is used for affecting at least one gene product. 
     
     
         44 . A method of predicting a prognosis and/or selecting a treatment to a subject comprising:
 i) determining a NAV3 copy number change in a biological sample from a subject;   ii) determining overexpression of at least one gene or gene product selected from IL23R, GnRHR, beta-catenin and those listed in tables 8-12, in the biological sample or another biological sample from the subject; and   iii) predicting a prognosis and/or selecting a treatment to a subject to the subject having both a NAV3 copy number change and overexpression of at least one gene or gene product selected from IL23R, GnRHR, beta-catenin and those listed in tables 8-12 in the sample(s).   
     
     
         45 . A method according to  claim 36 , wherein the NAV3 copy number change is caused by a deletion, amplification or translocation of NAV3 gene or major part of it. 
     
     
         46 . A method according to  claim 37 , wherein the NAV3 copy number change is caused by a deletion, amplification or translocation of NAV3 gene or major part of it. 
     
     
         47 . A method according to  claim 44 , wherein the NAV3 copy number change is caused by a deletion, amplification or translocation of NAV3 gene or major part of it. 
     
     
         48 . A method to  claim 36 , wherein the tumor is a colorectal tumor, brain tumor or tumor of epidermal keratinocytes. 
     
     
         49 . A method to  claim 37 , wherein the tumor is a colorectal tumor, brain tumor or tumor of epidermal keratinocytes. 
     
     
         50 . A method to  claim 44 , wherein the tumor is a colorectal tumor, brain tumor or tumor of epidermal keratinocytes. 
     
     
         51 . A method according to  claim 36 , wherein the tumor is a carcinoma. 
     
     
         52 . A method according to  claim 37 , wherein the tumor is a carcinoma. 
     
     
         53 . A method according to  claim 44 , wherein the tumor is a carcinoma. 
     
     
         54 . A method according to  claim 36 , wherein the brain tumor is a glioma. 
     
     
         55 . A method according to  claim 37 , wherein the brain tumor is a glioma. 
     
     
         56 . A method according to  claim 44 , wherein the brain tumor is a glioma. 
     
     
         57 . A method according to  claim 37 , wherein the gene(s) and/or gene product(s) is activated, inactivated, overexpressed or underexpressed, or amount of the gene product is increased or decreased. 
     
     
         58 . A method according to  claim 44 , wherein the gene(s) and/or gene product(s) is activated, inactivated, overexpressed or underexpressed, or amount of the gene product is increased or decreased. 
     
     
         59 . A method according to  claim 36 , wherein a presence of a tumor with a NAV3 copy number change and with overexpression of at least one gene or gene product selected from IL23R, GnRHR, beta-catenin and those listed in tables 8-12 is associated with lymph node metastases, high grade malignancy and/or poor survival. 
     
     
         60 . A method according to  claim 37 , wherein a presence of a tumor with a NAV3 copy number change and with overexpression of at least one gene or gene product selected from IL23R, GnRHR, beta-catenin and those listed in tables 8-12 is associated with lymph node metastases, high grade malignancy and/or poor survival. 
     
     
         61 . A method according to  claim 44 , wherein a presence of a tumor with a NAV3 copy number change and with overexpression of at least one gene or gene product selected from IL23R, GnRHR, beta-catenin and those listed in tables 8-12 is associated with lymph node metastases, high grade malignancy and/or poor survival. 
     
     
         62 . A method according to  claim 36 , wherein the gene or gene product is IL23R or/and GnRHR or a protein. 
     
     
         63 . A method according to  claim 37 , wherein the gene or gene product is IL23R or/and GnRHR or a protein. 
     
     
         64 . A method according to  claim 44 , wherein the gene or gene product is IL23R or/and GnRHR or a protein. 
     
     
         65 . A diagnostic kit comprising tools for detecting a NAV3 copy number change in a biological sample and tools for detecting overexpression of at least one gene or gene product selected from IL23R, GnRHR, beta-catenin and those listed in tables 8-12 in a biological sample.